On January 10, 2014, FDA issued a final rule amending the PMA regulations to require inclusion of information relating to pediatric subpopulations that suffer from the disease or condition that a device is intended to treat, diagnose, or cure, and the number of affected pediatric patients. These requirements are mandated by section 515A of the Federal Food, Drug, and Cosmetic Act (FDC Act), added by the Food and Drug Administration Amendments Act of 2007 (FDAAA). This information will be included in the annual reports submitted to Congress by FDA as required by section 515A(a)(3) of the FDC Act, which must contain the number of approved devices for which there is a pediatric subpopulation that suffers from the disease or condition that the device is intended to treat, diagnose, or cure, and the review time for each such device application.

Implementation of the final rule comes after FDA published a proposed rule and companion direct final rule on April 1, 2010. Due to receipt of significant adverse comments, FDA withdrew the direct final rule. After withdrawal of the rule, FDA issued a supplemental notice of proposed rulemaking on February 19, 2013, to seek public comment on the re-drafted proposed rule. We previously posted on this issue here. FDA received four additional comments on the proposed rule after withdrawing the direct final rule.

As mandated by section 515A(c) of the FDC Act, “pediatric subpopulation” is defined to have the same meaning given to the term in section 520(m)(6)(E)(ii), namely, to include one of the following populations: neonates, infants, children, or adolescents. Though section 515A does not define the age group intended to be included in “pediatric patients,” section 520(m)(6)(E)(i) defines pediatric patients to include those who are 21 years of age or younger at the time of diagnosis or treatment. FDA is adopting this same definition of “pediatric patients” for purposes of section 515A, despite comments suggesting that age 18 should serve as the upper bounds for pediatric patients.

Perhaps the greatest change made from the proposed to final rule was elimination of language in the proposed rule requiring applicants to include “potential pediatric uses” in their submissions rather than actual, known pediatric uses. After significant feedback from industry—and, perhaps, a closer look at the language of section 515A—FDA concluded that “section 515A of the FD&C Act does not require sponsors to speculate as to possible pediatric uses and possible subpopulations.” Of course, if sponsors wish to include that information, FDA “would find the information useful in support of advancing pediatric device development.”

Another change from the proposed to final rule is the submission types that must include the pediatric information. As provided in the statute, both the proposed and final rules state that section 515A applies to PMAs, HDEs, and PDPs, but there was some question as to the extent to which the pediatric information requirement applies to PMA supplements. Originally, FDA proposed that it would apply only to the subset of PMA supplements that propose a new indication for use. In the final rule, however, FDA states that, to be consistent with the statutory requirements, the requirement applies to all PMA supplements. At the same time, FDA notes that, consistent with the statute, it does not consider 30-day notices submitted under 21 C.F.R. § 814.39(f) to be PMA supplements for purposes of the final rule. Additionally, if an applicant who previously submitted the required pediatric information later submits a PMA supplement, it may include the previously submitted information by reference rather than providing the same information. If additional information about pediatric use has become “readily available” since the prior submission, that information should be included.

FDA has defined “readily available” to mean “available in the public domain through commonly used public resources for conducting biomedical, regulatory, and medical product research.” 21 C.F.R. § 814.3(t). In its draft guidance issued on the same day as the supplemental notice of proposed rulemaking, FDA expanded on this definition of “readily available” by providing examples, including “bibliographic databases of life sciences and biomedical information (such as MEDLINE and PubMed) and online scientific and medical publishers (such as the Public Library of Science (PLoS) and the Cochrane Library).” Presumably these examples will be present in the final guidance FDA states it will be issuing on this subject.

What FDA still has not answered is how it will use this pediatric information (other than to provide the report to Congress). As we noted in our blog post about the supplemental notice of proposed rulemaking, FDA stated in the draft guidance that its intent is to use the information to “coordinate efforts of stakeholders, device manufacturers and FDA staff to promote new device development and proper labeling of existing medical devices for pediatric use.” Perhaps the final guidance will clarify more precisely what this means.